What is EQA

Introduction

Over the years the American term proficiency testing (PT) has to some extent become synonymous with the European term of External Quality Assessment (EQA) and most laboratories have regarded the difference in terminology as one of the many vagaries of American English. 

However, a recent document published by the International Federation of Clinical Chemistry (IFCC), Education and Management Division, Committee of Analytical Quality challenges this statement. The Guidelines for the Requirement for the Competence of EQAP organizers clearly differentiates between the two [1].

The voluntary guidelines are directed to External Quality Assurance Program (EQAP) organizers to demonstrate competence by formal compliance with internationally acceptable requirements.

The guide is essentially based on ISO 43-1: 1997; ISO EN/IEC 17025: 1999; ISO 9000: 1994; ILAC G13: 2000; and CPA(EQA) [2-6]. A new terminology has emerged from the document of EQAP.

Definitions

Proficiency Testing (PT) is generally accepted as the term used in North America. The main focus of PT is essentially on the performance evaluations for regulatory purposes. Successful participation for laboratory accreditation is required by several US institutions such as the Centers for Medicare & Medicaid Services (CMS), the Joint Commission on Accreditation of Healthcare Organizations (JCAHO) and the College of American Pathologists (CAP). 

To pass proficiency testing, clinical laboratories must meet desirable standards laid down under the Clinical Laboratory Improvement Act (CLIA) [7].

Due to sanctions, PT schemes have to respect current analytical performance and therefore have wide acceptability limits. The fact that a laboratory may lose their license if they do not pass PT may influence the use of special practices for EQA samples [8].

A major limitation of the PT scheme is the tendency to maintain the quality at a certain level and they are unable to stimulate improvement of quality above this level [9,10].

External Quality Assessment Scheme (EQAS) is the general term used in Europe and South America.

EQAS focuses also on performance evaluations but the purpose of the scheme is educational. With the exception of Germany, there is no link between the results obtained in Western Europe and the condition of the reimbursement of tests. EQA will only reflect routine quality if all users are allowed to treat the EQA samples in the same way as patient samples, even with the risk of making a mistake. 

Since there are no sanctions, more stringent acceptability limits can be used and should produce a more realistic reflection of quality of lab performance. 

Acceptance limits based on biological variation and clinical decision limits can therefore be used to promote awareness of analytical deficiencies and stimulate method improvement. Interference studies and specificity studies are often undertaken in these schemes. 

In Europe there is an increase in the number of schemes that are emphasizing quality improvement through well-designed educational schemes and focus is on Quality Assurance rather than Assessment. The IFCC have therefore added another terminology to differentiate these schemes from the traditional EQAS.

External Quality Assurance Program (EQAP) is an interlaboratory comparison designed and operated to assure one or more of the following aspects, which will be described in the following sections:

• Participant performance evaluation
• Interpretation (including advice to the clinician on laboratory requests and diagnosis).
• Method performance evaluation.
• Postmarketing vigilance of in vitro diagnostic devices [11]
• Continuous education, training and help.

The primary intention of the activities of an EQAP in laboratory medicine shall be to support quality improvement of the services provided by the participating laboratories for the benefit of the patient.

Participant performance evaluation

This is essentially covered by both PT and EQA and is an evaluation of a participant’s measuring performance compared with other laboratories using the same methods. International and regional schemes can be used to assess one or more of the following [12]:

1. The quality of the analytical performance of the participant’s laboratory
2. The state of the art of participating laboratories
3. Intralaboratory variation
4. Interlaboratory variation
5. Relationship between calibration procedures and analytical results
6. Relationship between analytical procedures and results
7. Relationship between commercial reagents and results
8. Relationship between analytical instruments and results
9. State-of-the-art values for concentration of the analytes
10. Systematic deviations for the individual laboratory from state-of-the-art values or reference target values

A well-designed EQA Scheme should provide information on most of the ten points.

Interpretation

Examples of Clinical Interpretation Schemes include UKNEQAS Clinical Cases, UKNEQAS Toxicology, WEQAS Porphyrin and WEQAS Macroprolactin.

In the WEQAS Porphyrin Scheme the analytical and interpretative elements are examined. The following is an example of the clinical information distributed together with an EQA sample and the interpretation, as it should look according to an expert advisor:  

A blind sample is distributed along with clinical information, e.g. a urine sample with a total porphyrin concentration of 1400 nmol/L was distributed along with the following clinical information: “46-yr-old gentleman complaining of skin fragility and blistering lesions on the backs of his hands.”

The correct interpretation is given by an expert advisor and is made available to all participants along with a summary of the responses. Key phrases used by the expert (in bold in the example) are used to evaluate the responses.

Expert report comment Raised urinary porphyrin requires further investigation. Please send faeces (approx. 5 g) and EDTA blood. The raised urinary porphyrin is very suggestive that one of the cutaneous porphyrias is responsible for the patient’s skin lesions (which are typical). Confirmation of this and identification of the type of porphyria requires fractionation of the individual porphyrins in urine and stool and examination of plasma by fluorescence emission spectroscopy. This will probably entail referral to a specialist laboratory. All three specimens should be sent. It is particularly important to differentiate between cutaneous porphyrias in which potentially fatal acute attacks may occur (variegate porphyria and hereditary coproporphyria) and those in which they do not (porphyria cutanea tarda and congenital erythropoietic porphyria). Furthermore effective treatments exist for porphyria cutanea tarda but not the other types.

Summary of results 45 out of the 73 laboratories, (62 %) would have carried out the appropriate further investigation on all three samples, whilst 27 % would have carried out selective analysis of either blood urine or feces, eight would have also carried out Urine PBG on the sample. Three would have referred the sample, two laboratories would have investigated for family history and two for alcohol abuse.

Method performance evaluation

Laboratories are recommended to use in vitro diagnostic devices (IVDs) according to the manufacturer’s instructions. This evaluation requires the use of sample material as close as possible to patient samples. By comparing a homogeneous group of users of the same IVD the method performance can be evaluated [13]. This type of evaluation has proved to be particularly difficult in blood gas analysis due to the inherent instability of the patient sample. Over the last few years the WEQAS Blood Gas Scheme conducted studies to assess the performance of routine blood gas analyzers in the UK using a tonometered whole-blood material [14].

The use of material as close as possible to the patient sample minimizes any matrix effect and allows the assessment of accuracy. 

By using dedicated designs and samples, EQA can be used for studying robustness of methods, sensitivity to interferences, linearity, recovery, specificity and also pre- and postanalytical factors. Examples are found in UKNEQAS Steroid Hormones, WEQAS Mainline Chemistry, and WEQAS Lipid Scheme.

The WEQAS Lipid Scheme recently carried out an interference study to investigate the effect of a turbid, lipemic (chylomicron) sample on the performance of the major analyzers for lipid analysis.

Material The sample was a serum pool prepared from six fresh blood donations. All six samples appeared grossly lipemic and on standing had a significant chylomicron layer. The donations were pooled, gentamicin added, mixed well and aliquotted immediately. Unlike the other WEQAS pools, this pool was not filtered as this can decrease the triglyceride concentration. The aliquots were stored at –70 ºC until dispatch. Results For cholesterol a much wider interlaboratory variation was observed for the chylomicron sample compared with a concentration-matched pool analyzed at the same time. The majority of the cholesterol oxidase methods were affected.   For triglyceride a wider interlaboratory variability was observed for the majority of methods.  HDL appeared to be least affected by turbidity.   Preanalytical effects such as inadequate mixing of sample, variable time of analysis resulting in separation of chylomicron layer, and analyzer sampling technique can also be tested when dedicated EQA samples are designed.

Postmarket vigilance of IVD Directive (prEN 14136)

EQAS is able to contribute to postmarketing monitoring of IVD MD as mentioned in Directive 98/79/EC on IVD MD [15] to the benefit of both manufacturers and users. A well-designed scheme can provide data of comparison between new or established analytical procedures; demonstrate transferability of procedures; and disclose deficiencies of the IVD over long-term use. The use of repeat samples can demonstrate reproducibility and the effect of changes in the property of the IVD.

An important function of EQAS is to provide evidence of trueness of results through the use of appropriate samples analyzed by reference methods and to identify possible deficiencies of the IVD.

Where EQAS data indicate an apparent problem, the situation should be investigated further.

EQA Schemes play an important role in the continuous education of laboratory staff. The “non-profit”-making schemes in the UK, WEQAS and UKNEQAS have played key roles in Regional and National Audit, promoted harmonization of results, e.g. HbA1c standardization. 

WEQAS hosts annual scientific meetings covering topical, clinical and scientific issues, whilst UKNEQAS is coorganizer of the annual FOCUS meetings of the Association of Clinical Biochemists. WEQAS organizes training days on EQA interpretation and problem solving and supplements this with educational material via its website www.weqas.com.